Obesity / Immune Checkpoint Inhibitors / Colorectal Neoplasms · Journal article

Body mass index and dyslipidemia influence responses to anti-PD-1 immunotherapy in colorectal cancer.

Annals of Medicine · August 24, 2026

Promising Why this matters to you Expert discussion

Encouraging direction, but not yet definitive.

AI Summary

This retrospective cohort study of 142 CRC patients treated with anti-PD-1 immunotherapy reports that overweight/obesity (BMI ≥24 kg/m²) and dyslipidemia are associated with longer progression-free survival, with preliminary lipidomic evidence suggesting glycerophospholipid metabolism as a mechanistic pathway. The finding is hypothesis-generating rather than confirmatory, lacks a control comparator, and requires prospective validation before clinical application as a biomarker or therapeutic target.

What was studied

Retrospective cohort study. Colorectal cancer patients treated with anti-PD-1 immunotherapy who completed ≥2 cycles of therapy (n=142); eligibility criteria and exclusion criteria not detailed in abstract.. Intervention: Anti-PD-1 immunotherapy. Compared with: Stratification by BMI category and dyslipidemia status; no separate control group. n = 142. Not stated.

Key findings

Patients with BMI ≥24 kg/m² showed significantly longer PFS than normal BMI counterparts (p = 0.001) Multivariate analysis confirmed BMI as an independent prognostic factor for PFS Patients with dyslipidemia exhibited extended PFS (numerical comparison not provided)

Safety

Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.

Who this may help

If confirmed prospectively, BMI and dyslipidemia status might help stratify CRC patients for anti-PD-1 efficacy and identify candidates for lipid-modulating combination strategies. However, the counterintuitive finding that obesity improves immunotherapy response contradicts established obesity-cancer harm literature and requires mechanistic validation before influencing clinical practice.

Plain-language summary

A retrospective single-centre cohort study identifies BMI and dyslipidemia as associations with improved PFS in anti-PD-1-treated CRC, supported by exploratory lipidomic profiling, but lacks a control arm and prospective design to establish causation or clinical utility.

Study design

As stated by the source record.

MethodsCRC patients receiving anti-PD-1 therapy were stratified by BMI (≥24 vs <24 kg/m²) and dyslipidemia status. Progression-free survival was assessed and compared between groups. Multivariate analysis was performed to identify independent prognostic factors. Pre-treatment plasma samples from recurrence and non-recurrence subgroups underwent lipidomic profiling using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify metabolic associations.

DesignRetrospective cohort study

PopulationColorectal cancer patients treated with anti-PD-1 immunotherapy who completed ≥2 cycles of therapy (n=142); eligibility criteria and exclusion criteria not detailed in abstract.

Sample size142

InterventionAnti-PD-1 immunotherapy

ComparatorStratification by BMI category and dyslipidemia status; no separate control group

SettingNot stated

Reported figures

Quoted from the source exactly as published.

Sample size142

BMI threshold for improved PFS≥24 kg/m²

p-value for PFS difference by BMI0.001

Clinical bottom line

Caveats

Retrospective design without concurrent control or blinding; no adjustment for potential confounders (treatment line, tumour mutation burden, microsatellite instability status, baseline performance status).
Absolute PFS values and hazard ratios not reported; only p-value given for BMI stratification.
Lipidomic findings are exploratory biomarkers; no functional validation or mechanistic proof of glycerophospholipid involvement in immunotherapy response.
Subgroup analysis (JAK1/2, B2M wild-type) not powered; generalizability unclear because single-centre study and BMI criteria derived from Chinese population norms.

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

moderate

Retrospective cohort with stratified analysis; no randomisation or blinded outcome assessment.

Directness

moderate

Addresses clinical outcome (PFS) in CRC patients on anti-PD-1; lipidomic findings are exploratory biomarkers.

Consistency

limited

Single study; no mention of prior evidence or replication; direction contradicts obesity-harm paradigm in oncology.

Risk of bias

limited

Retrospective design; no blinding reported; potential confounding by treatment line, performance status, tumour characteristics.

Sample adequacy

moderate

142 patients analysed; adequate for stratified PFS analysis but small for robust subgroup claims (JAK1/2, B2M wild-type).

Source abstract

Background. Obesity is one of the primary risk factors for colorectal cancer (CRC) development, but the impact of obesity on therapeutic responses to anti-programmed cell death protein 1 (PD-1) immunotherapy in CRC remains unclear. This retrospective study investigates relationships between body mass index (BMI), dyslipidemia, and clinical characteristics in immune checkpoint inhibitors (ICIs)-treated CRC patients, while analyzing associated metabolic variations.Methods. Progression-free survival (PFS) was assessed in CRC patients receiving anti-PD-1 therapy, categorized by BMI and dyslipidemia status. Comprehensive lipidomic profiling was performed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify metabolic mechanisms underlying therapeutic responses.Results. This study enrolled 142 CRC patients who completed ≥ 2 cycles of anti-PD-1 therapy. Patients with BMI ≥ 24 kg/m2 (overweight per Chinese criteria) showed significantly longer PFS compared to normal BMI counterparts (p = 0.001). Multivariate analysis confirmed BMI as an independent prognostic factor for PFS. Moreover, patients with dyslipidemia exhibited extended PFS. Additionally, lipidomic analysis revealed differential pre-treatment levels of phosphatidylcholine (PC), phosphatidylethanolamine-ether (PE-O) and carnitine between the recurrence (R) and non-recurrence (NR) groups, accompanied by an enrichment trend in glycerophospholipid metabolism.Conclusion. Our findings show that obesity correlates with enhanced ICIs efficacy in CRC patients, potentially mediated through glycerophospholipid metabolic reprogramming. Furthermore, this association is more pronounced in the janus kinases 1/2 (JAK1/2) and β2-microglobulin (B2M) wild-type subgroup. These results support the potential utility of BMI as a predictive biomarker and highlight the need for further exploration of lipid-modulating combination therapeutic strategies.

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Shi-Hong ChenObesityWu JiangImmune Checkpoint InhibitorsChen-Zhi ZhangColorectal NeoplasmsZhen-Lin HouColorectal CancerImmunotherapyLe-En LiaoProgrammed Cell Death 1 ReceptorKai Han